RESUMEN
Since the start of the COVID-19 outbreak, pharmaceutical companies and research groups have focused on the development of vaccines and antiviral drugs against SARS-CoV-2. Here, we apply a drug repurposing strategy to identify drug candidates that are able to block the entrance of the virus into human cells. By combining virtual screening with in vitro pseudovirus assays and antiviral assays in Human Lung Tissue (HLT) cells, we identify entrectinib as a potential antiviral drug.
Asunto(s)
Benzamidas/farmacología , Tratamiento Farmacológico de COVID-19 , Indazoles/farmacología , SARS-CoV-2/efectos de los fármacos , Animales , Antivirales/farmacología , Benzamidas/metabolismo , COVID-19/metabolismo , Línea Celular , Chlorocebus aethiops , Evaluación Preclínica de Medicamentos , Reposicionamiento de Medicamentos/métodos , Humanos , Indazoles/metabolismo , Pulmón/patología , Pulmón/virología , Simulación del Acoplamiento Molecular , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidad , Células Vero , Acoplamiento Viral/efectos de los fármacosRESUMEN
G protein-coupled receptors (GPCRs) are intensively studied due to their therapeutic potential as drug targets. Members of this large family of transmembrane receptor proteins mediate signal transduction in diverse cell types and play key roles in human physiology and health. In 2013 the research consortium GLISTEN (COST Action CM1207) was founded with the goal of harnessing the substantial growth in knowledge of GPCR structure and dynamics to push forward the development of molecular modulators of GPCR function. The success of GLISTEN, coupled with new findings and paradigm shifts in the field, led in 2019 to the creation of a related consortium called ERNEST (COST Action CA18133). ERNEST broadens focus to entire signaling cascades, based on emerging ideas of how complexity and specificity in signal transduction are not determined by receptor-ligand interactions alone. A holistic approach that unites the diverse data and perspectives of the research community into a single multidimensional map holds great promise for improved drug design and therapeutic targeting.